This proposal will investigate chiral recognition between macrocyclic antibiotics and enantiomeric compounds using capillary electrophoresis and use the results obtained in a variety of theoretical and practical ways. By understanding these chiral interactions we will be able to attain several goals: 1) the rapid and efficient separation of enantiomeric and diastereomeric drugs with macrocyclic antibiotics; 2) identify experimental parameters which have the greatest effect on enantioseparations; and 3) identify new chiral selectors to extend the scope of enantioseparations. The importance of this work to the health related fields becomes evident when one realizes that over half of the top 200 drugs prescribed contain at least one chiral center and that approximately 75 to 90 percent of these are marketed as racemates. It is well known that enantiomers of many drugs differ in potency, pharmacological actions, and biodistribution. A number coated capillary columns will be made to eliminate wall adsorption effects and to suppress electroosmotic flow. Using these capillaries, structure-interactions between a series of structurally related enantiomers and various macrocyclic antibiotic will be investigated. Binding constants and free energies will be calculated between macrocyclic antibiotics and these enantiomers to evaluate and understand chiral recognition. Although the main emphasis of this project will be on the theoretical aspects, the knowledge gained will compliment the practical applications of capillary electrophoresis developed in this study.